tbuckley/cabot-search huggingface dataset:
AB0816 COMORBIDITY AND THE USE OF BIOLOGICAL THERAPY IN AXIAL SPONDYLOARTHRITIS, IS THERE ANY IMPACT?
Authors: K. Tahir, N. Akasbi, I. El Mezouar, T. Harzy
Journal: Annals of the Rheumatic Diseases (2022)

Background Spondyloarthritis (SpA) is a chronic inflammatory rheumatism that can be associated with a lot of comorbidities. Comorbidity seems to be a factor that is can influence the treatment tactics. Objectives The aims of our study were to describe the prevalence of commonly reported comorbidities in spondyloarthritis and to study the influence of comorbidity on the prescription of biological therapies in patients with SpA. Methods A retrospective study was conducted in a single rheumatology hospital in Morocco, including patients diagnosed as having SpA according to ASAS criteria 2010, during a period of 9 years. Comorbidity data were obtained through careful examination of the history and medical records. The Charlson comorbidity index [1] calculated for every patient. Results 375 patients were included in the study. 206 (54,9%) women, mean age 46.8±14,0 years. 105 patients were treated with biologic therapy (28%), in majority with TNF alpha inhibitors (99 patients). 188 (50,1%) patients had Charlson comorbidity index =1. The most common comorbidities were type 2 diabetes (12% patients), cancer (4,5%), chronic liver disease (2,9%), chronic kidney disease (2,1%), peptic ulcer (1,6%), ischemic heart disease (1,3%). Mean Charlson index was 1,14 ± 1,56 in total group; it was significantly lower in patients who were treated with biological therapy (0,6 ± 1,03) than in biologic naïve SpA (1,35 ± 1,68), p=0,0001. Biologics were prescribed in 66,7% of patients without comorbidities, in comparison with 17,1% of patients with Charlson comorbidity index = 1, 8,6% with Charlson comorbidity index = 2 and 6,8% of patients with Charlson index = 3 or more. Conclusion Comorbidities are common in SpA and have a direct impact on the use of biological therapy. The development of therapeutic strategy for treating comorbid conditions is a must to achieve therapeutic goals in SpA. References [1]Charlson E M et al. A new method of classifying prognostic comorbidity in longitudinal studies:development and validation. J Chronic Dis. 1987;40(5):373-83. Disclosure of Interests None declared
AB1045 QUALITY OF LIFE IN PATIENTS WITH GOUT TAKING URATE-LOWERING DRUGS, DEPENDING ON THE ACHIEVEMENT OF THE TARGET LEVEL OF SERUM URIC ACID
Authors: M. Chikina, O. Sheliabina, M. Eliseev
Journal: Annals of the Rheumatic Diseases (2022)

Background Intake of urate-lowering drugs (ULD) leads to an improvement in the quality of life (QoL) in pts with gout. However, it is not clear to what extend the QoL is changed in pts who did not achieve the target level of serum uric acid (sUA). Objectives to evaluate the dynamics of the QoL in pts, taking ULD, who have achieved and have not achieved the target sUA level. Methods 98 pts with gout were included in the prospective study. The follow-up period was 24 months, allopurinol or febuxostat at doses sufficient to achieve the target sUA level (&lt;360 µmol/l) were used. The maximum daily dose of allopurinol was 900 mg/day, febuxostat - 120 mg/day. Pts who did not achieve the target sUA level continued taking ULD at the maximum dosages. The values of the Qol in dynamics were calculated using the SF-36v2 questionnaire. The assessment of the QoL was carried out separately in pts who achieved and did not achieve the target level of sUA. The frequency of exacerbations of arthritis was also assessed. Statistica 12.0 package was used for statistical data processing. Results 69 of 98 (70%) pts achieved the target sUA level, wherein allopurinol was taken by 46 pts, febuxostat – 34 pts. Pts who achieved the target level of sUA after 6 mo. of ULD usage, demonstrated a significant improvement in the physical health (PH), including physical functioning (PF), role limitations due to physical functioning (RP), general health (GH), as well as vitality (VT) (p&lt;0.05 for all). After 12 and 24 mo. improvement was achieved in RH, GH and PF (p&lt;0.01), RP, bodily pain intensity (BP) and VT (p&lt;0.05). General mental health (MH), role-emotional functioning (RE) and social functioning (SF) were unchanged throughout the study. Pts who did not achieve the target sUA level after 6 and 12 mo. significantly improved: PF, RP (p&lt;0.05 for all). After 24 months, for all QoL parameters, the values did not differ from the initial ones. The frequency of arthritis exacerbation in pts who achieved the target sUA level decreased from 3.1±1.6 cases per year to 0.9±1.1 cases per year (p=0.0013); in those who did not achieve - from 3.1±1.9 cases per year to 2.4±1.6 cases per year (p=0.047). Conclusion : The QoL in gout pts who achieved target sUA level continues to improve during the first year of ULD intake. Even if the target sUA level is not achieved, the QoL of patients with gout treated with ULD remains stable for at least 2 years of therapy. This predetermines the need to use maximum daily doses of ULD, even if the target serum UA level is not achieved. Disclosure of Interests Maria Chikina: None declared, Olga Sheliabina Speakers bureau: Berlin Chemie Menarini Group, Maxim Eliseev Speakers bureau: Berlin Chemie Menarini Group, Sobi, EGIS, CSC, MosFarma, Alium Group
AB1069 URIC ACID LEVELS IN RELATION TO FASTING BLOOD GLUCOSE AND HbA1c
Authors: F. Fhima, N. El Amri, D. Khalifa, A. Ben Abdelkrim, S. Lataoui, B. Ben Abdallah, K. Baccouche, E. Bouajina, K. Ach
Journal: Annals of the Rheumatic Diseases (2022)

Background Hyperuricemia is reported to be a risk factor for the development of type 2 diabetes (T2D) and prediabetes. Objectives To determine the prevalence of HU and gout in T2D and prediabetes and to study the relationship between HU, gout, T2D and prediabetes. Methods A cross-sectional study was conducted beween January 2021 and June 2021 in the Rheumatology and endocrinology departments of Farhat Hached Hospital. Patients who fulfilled the diagnosis of diabetes or prediabetes according to the American Diabetes Association guidelines of 2021 were included. Uric acid levels were also assessed and HU was defined as uric acid levels ≥ 360 µmol/l in women and ≥ 420 µmol/l in men. Diagnosis of gout was based on the ACR/EULAR 2015 classification. Results One hundred fifty-one patients having T2D and 46 prediabetic patients were included. The mean of age in both groups was 61 and 54 years respectively. Prevalence of HU was 26.1% in prediabetic while it was 17.2% in the group of T2D with no statistical relevance (p=0.182). No difference related to gender was observed in both groups. The prevalence of gout was higher in the prediabetes group (15.2%) compared to the T2DM group (6%) but without significant difference (p=0.062). Uric acid levels were remarkably higher in prediabetic patients (mean=324,3 µmol/l) compared to patients having T2D (median=278 µmol/l) with a significant statistical difference (p=0.022). No association was identified between HU, fasting blood glucose and HbA1C in the two groups. However, uric acid levels are inversely proportional to fasting blood glucose (p=0,001) and HBA1C (p=0.001) in all patients. Conclusion Individuals with moderately elevated HbA1c and fasting glucose levels (prediabetes) may be at a higher risk of HU, whereas individuals with diabetes or elevated HbA1c levels may have a normal uricemia. This could be explained by the GLUT-9 transporter regulation in the renal proximal tubule that blocks the absorption of uric acid when glycosuria is present. References [1]Choi HK, Ford ES. Haemoglobin A1c, fasting glucose, serum C-peptide and insulin resistance in relation to serum uric acid levels--the Third National Health and Nutrition Examination Survey. Rheumatology. 29 janv 2008;47(5):713-7. [2]van der Schaft N, Brahimaj A, Wen K, Franco OH, Dehghan A. The association between serum uric acid and the incidence of prediabetes and type 2 diabetes mellitus: The Rotterdam Study. Hribal ML, éditeur. PLOS ONE. 20 juin 2017;12(6):e0179482. Disclosure of Interests None declared
AB0302 DIASTOLIC DYSFUNCTION IN RHEUMATOID ARTHRITIS PATIENTS: A COMPARATIVE CROSS-SECTIONAL STUDY
Authors: M. Brahem, H. Ibn Hadj Amor, R. Sarraj, S. Kraiem, R. Rouabhia, E. Hmaier, A. Ben Salem, R. Grassa, G. Haj Mbarek, H. Hachfi, Y. Mohamed
Journal: Annals of the Rheumatic Diseases (2022)

Background Cardiac failure is an independent risk factor for mortality in Rheumatoid arthritis (RA) and diastolic dysfunction (DD) may act as a precursor for cardiac failure. Objectives The aim of our study is to determine the frequency of diastolic dysfunction in rheumatoid arthritis (RA) patients compared to a control group and to focus on associated factors. Methods This was a comparative cross-sectional study, including patients diagnosed with RA according to the ACR/EULAR 2010 criteria and control subjects. Each patient underwent transthoracic echocardiography and the DD was assessed by E/A and E/a ratio. Results Seventy-two patients with RA and 72 control subjects were included. In our study, there was a clear female predominance in both groups (93.1% vs 94.4%). The mean age of RA patients was 52.9 ± 11.72 years [21-75 years] and that of the control group was 49.26 ± 10.74 years [19-76 years]. In RA group, the mean duration of disease was 12.4 ± 9.9 years [6 months-40 years]. The means of DAS 28 (CRP), DAS 28 (ESR) and HAQ score were respectively 3.4 ± 1.4 [1.2-6.7]; 3.9 ± 1.4 [1.4-7.4] and 0.9 ± 0.7 [0-2.5]. 51.4% of patients had an increased ESR and 37.5% of cases had an increased CRP (CRP&gt;6). In RA group, DD was present in 26 patients (36.1% of cases). The mean value of the impaired E/A ratio was 0.7 ± 0.1 [0.4-0.9] and the mean value of the impaired E/a ratio was 9.8 ± 1.5 [8.5-14.4]. These patients (23 women and 3 men) had a mean age of 56 ± 10.4 years [33-74 years]. Among them, 7 patients had hypertension, 9 patients had cardiac symptoms, 21 patients had a long-standing RA, 17 patients had positive ACPAs and 11 patients had positive RF. In control group, DD was present in 10 patients (13.9% of cases). The mean value of the impaired E/A ratio was 0.6 ± 0.1 [0.4-0.9] and the mean value of the impaired E/a ratio was 9 ± 0.6 [8.4 to 10.1]. Left ventricular diastolic dysfunction was more frequent in RA patients compared with the control group with a significant difference (p&lt;0.01). No significant association was found between diastolic impairment and RA parameters. Conclusion Subjects with RA have a higher frequency of diastolic dysfunction than those without RA. Therefore, correct assessment of diastolic function should be considered of pivotal importance in the routine follow-up of RA patients. The identification of predictor factors requires further study. References [1]Cavazzana I, Vizzardi E, Franceschini F. Diastolic dysfunction in rheumatoid arthritis : Monaldi Arch Chest Dis 2019; 891137 2019;89. Disclosure of Interests None declared
Michael Servetus, Doctor of Medicine
Authors: Miguel Ángel Cobos Gil
Journal: JAMA Cardiology (2022)

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Squalene Epoxidase Metabolic Dependency Is a Targetable Vulnerability in Castration-Resistant Prostate Cancer
Authors: Xun Shangguan, Zehua Ma, Minghao Yu, Jie Ding, Wei Xue, Jun Qi
Journal: Cancer Research (2022)

Abstract Considering the dismal prognosis of castration-resistant prostate cancer (CRPC), it is critical to identify novel therapeutic targets in this disease. Malignant cells have metabolic dependencies distinct from their healthy counterparts, resulting in therapeutic vulnerabilities. Although PTEN and TP53 are the most frequently comutated or codeleted driver genes in lethal CRPC, the metabolic dependencies underlying PTEN/p53 deficiency-driven CRPC for therapeutic intervention remain largely elusive. In this study, PTEN/p53 deficient tumors were determined to be reliant on cholesterol metabolism. Moreover, PTEN/p53 deficiency transcriptionally upregulated squalene epoxidase (SQLE) via activation of sterol regulatory element-binding protein 2 (SREBP2). In addition, PTEN deficiency enhanced the protein stability of SQLE by inhibiting the PI3K/Akt/GSK3β-mediated proteasomal pathway. Consequently, SQLE increased cholesterol biosynthesis to facilitate tumor cell growth and survival. Pharmacologic blockade of SQLE with FR194738 profoundly suppressed the invasive program of CRPC. Collectively, these results demonstrate a synergistic relationship between SQLE and PTEN/p53 deficiency in CRPC development and progression. Therefore, pharmacologic interventions targeting SQLE may hold promise for the treatment of patients with CRPC. Significance: This study reveals PTEN and p53 deficiency confers a dependence on SQLE-mediated cholesterol metabolism, providing insights for new therapeutic strategies for treating castration-resistant prostate cancer.
POS1425 THE BURDEN OF OSTEOARTHRITIS ACROSS THE STATES OF INDIA, 1990–2019: FINDINGS FROM THE GLOBAL BURDEN OF DISEASE STUDY 2019
Authors: A. Singh, S. K. Das, A. Chopra, D. Danda, B. J. Paul, L. March, A. J. Mathew, P. Shenoy, C. Gotay, A. J. Palmer, B. Antony
Journal: Annals of the Rheumatic Diseases (2022)

Background Few studies have reported the burden of osteoarthritis (OA) in different parts of India. However, no study has reported the detailed estimates of incidence, prevalence, and years lived with disability (YLDs) and its trends for OA (and its various sites) across the states of India over a long period of time. Objectives We aim to describe the state-wise prevalence, incidence, and YLDs for osteoarthritis (OA) in India from 1990 to 2019 according to age and sex. Methods Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA –including knee OA, hip OA, hand OA, and other OA– was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, and YLDs modelled data using the methods reported in the GBD 2019 Study. All estimates are presented as counts and age-standardised rates per 100,000 population, with uncertainty intervals (UIs). Results Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI): 4,420–5,447) in 1990 to 5313 (95%UI: 4,799–5,898) in 2019, per 100,000. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1·48% (95%UI: 0·88–2·78) of all YLDs; increasing from 23rd most common cause in 1990 (1·25% (95%UI: 0·74–2·34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and YLDs for OA and knee OA were consistently higher in females than males. Uttar Pradesh (8.53 million (95%UI: 7.63–9.53), Maharashtra (6.37 million (95%UI: 5.75–7.06), and West Bengal (4.90 million (95%UI: 4.39–5.46) had the three highest levels of OA prevalence. Goa (5689 (95%UI: 5,125–6,282)), Rajasthan (5667 (95%UI: 5,097–6,305)), and Kerala (5658 (95%UI: 5,107–6,263)) had the highest age-standardised prevalence of OA in 2019, per 100,000 (Figure 1 A and B). Conclusion The burden and impact of OA in India are substantial and is increasing; however, it varied among states. Females were affected more commonly than males. Knee OA was the most prevalent site. With improvement in life expectancy and population ageing, greater increases are expected. Adopting suitable control and preventive community measures to reduce modifiable risk factors (such as obesity, injuries, occupational stress) are needed now to reduce the current and future burden of OA in India. Disclosure of Interests None declared
AB1282 OVARIAN RESERVE IN BEHCET’S DISEASE
Authors: Z. Alekberova, R. Goloeva, M. Cherkasova, A. Lila
Journal: Annals of the Rheumatic Diseases (2022)

Background Behcet’s disease (BD) is a multisystemic disease of unknown cause. Anti-Mullerian hormone (AMH) is one of the key parameters for assessing reproductive function and ovarian reserve. The levels of AMH correlates with the residual follicular pool in women of reproductive age. Objectives To assess AMH levels in BD female patients of child-bearing potential, and analyze the relationship between AMH levels and disease severity, as well as relationship between serum AMH levels and different therapeutic regimens. Methods The study group included 45 women with BD (according to ISGBD 1990 and ICBD 2014) aged 20-40 years, and the control group icluded 15 age-matching healthy women. Pts’ mean age was 31,3 [27;35] yrs, disease duration 6 [3;8] yrs. 17,8% pts had severe BD according to Ch.Zouboulis classification (due to generalized uveitis, retinal vasculitis and parenchymatous CNS lesions), 37,8% pts had a moderate disease, 44,4% pts had a mild disease with mainly dermal-mucous manifestations. AMH levels was measured using ELISA. AMH reference values ranged within 1.0-10.6 ng / ml. Values &lt;1.0 were interpreted as a decreased ovarian reserve. Results The mean levels AMH was 2.5 ng/ml in BD pts, and 3.1 ng/ml in control group, showing no statistical difference. A decrease in ovarian reserve (AMH less than 1.0 ng/ml) was observed with the same frequency 18% in patient’s vs. in control group 13%. In the analysis of AMH, depending on the severity of BD, a decrease in ovarian reserve was more often observed in patients with moderate and severe forms of BD. Table 1. AMH and severe BD severe mild, n=20 moderate disease, n=17 severe, n= 8 p АMH 2,7 [1,6-3,5] 2,5 [1,0-3,7] 1,9 [0,8;6,7] ns АMH &gt;1 ng/ml, % 10 23 25 0,02 There are no correlations of levels AMH with treatment of BD. A decrease in ovarian reserve was noted in two patients under 30 years old, one was 29 years old woman with “Neurobehcet” with two children, and the patient with BB+AS was not married, had no pregnancies, and received colchicine therapy for a long time. Two BD patients with low AMH had no pregnancies - unmarried, all other patients with reduced ovarian reserve had from 1 to 6 children. When analyzing the levels of AMH with the clinical picture and BD therapy, no correlations were found. Conclusion The average levels of AMH in women with BD and in the control group did not differ. A decrease in ovarian reserve (AMH less than 1.0 ng/ml) occurred with the same frequency in patients with BD and controls. A decrease in ovarian reserve was more often observed in patients with moderate and severe BD. References [1]Zouboulis C., Vaiopoulos G., Macromichelakis N. et al. Onset signs, clinical course, prognosis, treatment and outcome of adult patients with Adamantiades – Behcet’s disease in Greece. Clin.Exp.Rheum.2003, 21, (suppl.30) S19-S26. Disclosure of Interests None declared
POS0398 IDENTIFICATION OF THE HLA-B*51:01 IMMUNOPEPTIDOME IN BEHÇET’S DISEASE
Authors: Y. J. Lee, K. C. Cho, S. H. Kim, B. K. Cho, E. C. Yi, E. B. Lee
Journal: Annals of the Rheumatic Diseases (2022)

Background Immunopeptidomes are peptides, bound to human leukocyte antigens (HLA), that play a key role in immune responses. HLA-B*51:01 is an HLA allele associated with Behçet’s disease (BD) 1 . However, the characteristics and the role of HLA-B*51:01 immunopeptidome are not revealed in Behçet’s disease. Objectives To investigate the difference of HLA-B*51:01 immunopeptidome between Behçet’s disease and healthy controls (HCs) and to select candidate peptides which have a pathogenic role in Behçet’s disease. Methods HLA-bound peptide profiles were established through analysis of plasma samples from HLA-B*51:01–positive BD patients and HCs. HLA-class I molecules were immunoprecipitated, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed. Then, HLA-B*51:01–binding peptides were assessed in terms of binding affinity using NetMHCpan. Finally, the immunological characteristics of selected peptides were analyzed in BD patients and HCs, using ELISpot, flow cytometry, and dextramer staining. Results 2,306 peptides were present only in BD patients, while 3,145 peptides were detected only in HCs. Immunopeptidome of BD patients preferentially showed hydrophobic amino acids at amino acid position 2 (Figure 1). Ten peptides were selected which were confirmed to be preferentially expressed in BD patients compared with HCs. When bound to HLA-B*51:01 in monocyte-derived dendritic cells (Mo-DCs) or peripheral blood mononuclear cells, these peptides activated T cells and induced surface expression of CD69 and CD107, as well as the secretion of inflammatory cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Figure 1. Venn diagram of the identified 8–13-mer peptides and graphs showing the motif clusters. (A) Venn diagram showing the numbers of peptides detected by immunoprecipitation with BD patients or HCs. The number of peptides isolated with isotype antibodies were also depicted. (B) Motif clusters of human leukocyte antigen (HLA)-B*51:01-positive BD patients and HCs. Conclusion HLA-B*51:01 immunopeptidome can play a critical role in the development of BD by activating T cells and inducing the secretion of inflammatory cytokines. References [1]Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, et al. Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behcet’s disease susceptibility. Nat Genet 49 , 438-443 (2017). Disclosure of Interests Ye Ji Lee: None declared, Kyung-Cho Cho: None declared, So Hyun Kim: None declared, Byung Kyu Cho: None declared, Eugene C Yi: None declared, Eun Bong Lee Consultant of: EBL has acted as a consultant for Pfizer., Grant/research support from: EBL has received a research grant from GC Pharma, Handok Inc., South Korea.